Case Report: Callosal disconnection syndrome manifesting as mixed frontal-callosal-posterior alien hand syndrome following extensive corpus callosum infarct

Alien hand syndrome (AHS) is a rare neurological phenomenon first described by Van Vleuten over a century ago. The most widely recognized variants in literature are frontal, callosal, and posterior AHS. AHS due to the corpus callosum lesion can occur alone or as part of callosal disconnection syndrome (CDS). This report presents a unique CDS case manifesting clinical features from all three AHS variants, resulting from an extensive corpus callosum infarct. Our patient exhibited various clinical features from the three AHS variants, which include grasping, groping, and difficulty releasing objects from the hand (anterior); intermanual conflict (callosal); arm levitation, mild hemiparesis, and hemisensory loss (posterior). Additionally, the extensive disruption of the corpus callosal fibers produced neurological manifestations of CDS, such as cognitive impairment, ideomotor and constructional apraxia, behavioral disorder, and transcortical motor aphasia. We employed a range of rehabilitation interventions, such as mirror box therapy, limb restraint strategy, verbal cue training, cognitive behavioral therapy, bimanual hand training, speech and language therapy, and pharmacological treatment with clonazepam. The patient showed almost complete resolution of CDS and AHS features by nine months post-stroke Our case report highlights distinctive clinical variations of AHS and the challenging correlation between clinical manifestations and neuroanatomical substrates. Future studies are necessary to explore the intricate neural connections and the precise function of the corpus callosum. This can be achieved by combining comprehensive neuropsychological testing with diffusion tensor tractography studies. It is also essential to develop a validated tool to standardize AHS assessment. Finally, the scarcity of evidence in rehabilitation interventions necessitates further studies to address the wide knowledge gap in AHS and CDS management.


Introduction
The corpus callosum (CC) is the most extensive white matter bundle connecting cortical regions within the two cerebral hemispheres' frontal, parietal, occipital, and temporal lobes. 1 CC fibers contribute to the interhemispheric transfer of cognitive, somatosensory, motor, executive, and visual information. 2Communication disruption between cerebral cortical areas due to CC lesion causes callosal disconnection syndrome (CDS).The corpus callosum receives blood supplies from anterior communicating arteries (ACOM), the pericallosal artery, a branch of the anterior cerebral artery (ACA), and pericallosal branches from the posterior cerebral artery (PCA). 3Given the extensive blood supplies, CC infarcts are a rare occurance. 3,4e clinical presentation of callosal lesions in each individual is highly variable, depending on location and extent of the CC damage.Even if the lesion location and extent are similar, symptoms can vary widely. 2 Patients with a callosal lesion often exhibit severe clinical features 3 such as visual agnosia, apraxia, conductive aphasia, alexia, 5 tactile and visual anomia, neglect, agraphia, and the dissociative phenomenon commonly known as alien hand syndrome (AHS). 2 AHS is defined as involuntary, autonomous, apparently purposeful behaviors in which the affected limb is perceived as being controlled by an external force. 6It was first described by Van Vleuten 7 in 1907 in a patient with a left-hemisphere brain tumor that had invaded the corpus callosum and exhibited right-hand grasping.The following year, Goldstein 8 described a stroke patient exhibiting involuntary left-hand movements.Brion & Jedynak 9 coined the term 'alien hand' in 1972 to describe the experience of the hand as belonging to someone else, which was observed in three patients.
Three principal variants of AHS have been recognized; frontal, callosal, and posterior.The frontal variant typically affects the dominant hand 10 and is associated with lesions in the supplementary motor area (SMA), cingulate cortex, dominant medial prefrontal cortex, or the anterior corpus callosum. 11It is characterized by grasping, groping, or compulsive manipulation of tools.The alien hand is perceived as being unpleasant and evokes frustration and anxiety. 6The callosal variant, primarily arising from callosal damage, is characterized by intermanual conflict (IMC) 11 of the non-dominant hand, in which one hand acts at cross-purposes with the other, 6 likely due to the lack of activation or suppression of inhibitory patterns. 11Together, the frontal and callosal variants make up the anterior AHS.Posterior AHS, on the other hand, is caused by damage to the thalamus, posterolateral parietal, or occipital lobe 12 and is characterized by arm levitation, mild hemiparesis, hemispatial neglect, hemisensory loss, and sensory ataxia. 6 describe a case of CDS presenting as mixed AHS, cognitive impairment, ideomotor and constructional apraxia, behavioral disorder, and transcortical motor aphasia.This is the first report of AHS manifesting clinical features from all three variants.Our discussion delves into the distinctive clinical variations, the challenging correlation between clinical manifestations and neuroanatomical substrates, and the implementation of various rehabilitative strategies.

Case report
This research received ethics approval from the National Medical Research Register Malaysia (NMRR ID-22-02490-XLP).
A 57-year-old, right-handed female with risk factors of type II diabetes mellitus and hypertension presented with a sudden onset of left-sided body weakness and slurred speech.The Glasgow Coma Scale (GCS) was 15/15, and her blood pressures were normal.The medical research council (MRC) motor power scale indicated a 4/5 strength in her left upper and lower extremities.Computed tomography (CT) scan of the brain revealed an acute right temporal infarct.The following day, her GCS dropped to 10/15, accompanied by elevated blood pressure.A repeat CT scan was done urgently on the same day and displayed an evolution of the right temporal infarct and a new acute corpus callosum infarct extending from the right genu to the left side of the splenium (Figure 1 and Figure 2).Subsequent CT angiography (CTA) revealed short segment stenosis of the proximal M1 segment of the right middle cerebral artery (MCA), left fetal PCA,

REVISED Amendments from Version 1
This revised manuscript clarifies why neuropsychological evaluation and magnetic resonance imaging were not performed in this case report by expanding the study limitation paragraph.We have also included information requested by the reviewers, such as the timing of the repeat CT scan and the details of the type of sensory loss.Additionally, as noted by one of the reviewers, we have amended the manuscript to reflect that the earliest report of alien hand syndrome (AHS) was by Van Vleuten in 1907.Finally, we have expanded the discussion on arm levitation to include paroxysmal kinesigenic dyskinesia (PKD) as a possible alternative diagnosis to posterior AHS, explaining why the arm levitation in this case is more consistent with posterior AHS than with PKD.
Any further responses from the reviewers can be found at the end of the article and hypoplastic right posterior communicating (PCOM) artery.Three weeks post-stroke, she was transferred to the rehabilitation unit.

Inpatient rehabilitation
Upon assessment, the patient had global cognitive impairment with a baseline Mini-Mental State Examination (MMSE) score of 14/30.She displayed irritability and disinhibition, often shouting at or striking her caregiver without provocation.Moreover, she was uncooperative when her caregiver attempted to assist her with personal activities of daily living (pADLs), such as getting dressed and bathing.Her mood was labile, with inappropriate crying and laughing episodes, indicative of pseudobulbar affect (PBA).She also had transcortical motor aphasia, evidenced by limited spontaneous speech, difficulty retrieving known words (anomia) and initiating conversation, and long response delay.However,  reading and repetition were relatively preserved, and language comprehension was good.Additionally, there was leftsided hemisensory loss in both pin-prick and light touch sensation but intact proprioception, and there were no signs of hemineglect.
The patient's mildly paretic left upper extremity manifested abnormal and involuntary movements.It frequently counteracted her right hand's actions (IMC).For instance, the left hand prevented the right hand from bringing a spoon closer to her mouth while she fed herself.While the right hand attempted to pull up her pants, the left resisted.Additionally, the left hand exhibited independent and purposeless actions.It unintentionally searched for and grasped any objects within sight on the table during meals or therapy sessions (groping & grasping).The patient also struggled to release objects held by her left hand, even when applying force.The left hand failed to follow verbal commands or imitate visual cues (ideomotor apraxia).However, there was no right-left confusion, and the patient remained aware of the unwilled actions performed by her left hand.She expressed anger and frustration by slamming her left hand on the table or using her right hand to strike the left (auto-criticism).Notably, she did not deny ownership of her left hand and considered it part of her body.
The patient received a combination of rehabilitation interventions.During therapy sessions, her affected hand was placed inside a mirror box, preventing her from reaching for objects on the table.The mirror reflected the volitional movement of her right hand, providing the perception that she had control over her left hand's movement.Additionally, she was taught to keep the left hand in her pocket when it began to move unwillingly (limb restraint).The mirror box and limb restraint strategies were targeted to control the IMC, groping, and grasping.The caregiver received training on verbal cue strategies.She was instructed to verbally prompt the patient to complete her task whenever the IMC occurred.This continued until the patient could complete tasks with her right hand without verbal command.The strategy was also implemented during activities outside the therapy sessions.To alleviate her anger and frustration, the patient underwent cognitive behavioral therapy (CBT).Furthermore, she underwent speech and language therapy, bimanual hand training, pADLs, and ambulation training.Upon discharge (six weeks post-stroke), the patient was moderately dependent in pADLs and could ambulate using a quadripod under her caregiver's supervision.Her PBA had resolved, and her behavior became more manageable.

Outpatient rehabilitation
The caregiver reported a new symptom during the first outpatient review two months post-stroke.While walking, the patient's left hand would spontaneously raise (arm levitation), exhibiting shoulder abduction, elbow flexion, forearm supination, and a fisted hand position.Once elevated mid-air, the arm began shaking uncontrollably.The phenomenon occurred every time she walked, happening more than ten times per day.Groping, grasping, and IMC episodes continued to disrupt her daily activities.However, her speech had improved, with clearer spontaneous speech and shorter response delay.She was more cheerful and displayed appropriate behavior.Although her MMSE score had improved to 27/30, the findings from the visuospatial/executive domain of the Montreal Cognitive Assessment (MoCA) suggested constructional apraxia.To manage the worsening motor symptoms, we prescribed clonazepam 0.5 mg twice daily.The patient continued to receive all previously mentioned interventions as part of her outpatient treatment.
Three months post-stroke, the patient experienced significant improvements.The frequency of arm levitation, groping, and grasping episodes had reduced by 50%, and IMC had entirely resolved.She achieved independence in ambulation without needing a walking aid and could climb stairs while supervised by her caregiver, holding onto the rail for support.The patient could independently perform most pADLs, except for toileting, where she still required some supervision to ensure proper hygiene.Her behavior was appropriate, and the auto-criticism had ceased.To address the remaining arm levitation, groping, and grasping issues, we increased the clonazepam dosage to 1 mg twice daily, aiming for the complete resolution of these motor symptoms.
Six months post-stroke, the patient achieved complete independence in all aspects of pADLs and ambulation.Most CDS and AHS features had resolved, except for arm levitation.She was fully aware of her left arm's involuntary movement and would place it in her pocket when it began to raise during ambulation.The frequency of groping and grasping episodes had significantly reduced, occurring only once or twice per week, and no longer impairing functionally.Instead of feeling distressed, the patient now found the remaining symptoms amusing.By nine months post-stroke, no further improvements were observed, so the clonazepam treatment was discontinued.

Discussion
AHS has been a subject of intrigue in the neurological community since its initial description by Van Vleuten more than a century ago.It remains a relatively uncommon condition.To date, there have been fewer than 200 reported cases, 11 with 34 of them representing mixed variant AHS involving a combination of two of the three recognized variants (Table 1). 4,6, In tis report, we discuss an unprecedented case of AHS exhibiting features from all three variants, accompanied by several distinctive clinical and neuroanatomical variations: (1) The frontal variant symptoms, which were grasping, groping, and difficulty releasing objects from the hand, occurred in the patient's non-dominant hand, which is an unusual presentation.
(2) The arm levitation, a characteristic of the posterior AHS variant, manifested much later than the other clinical features, suggesting a potential temporal progression in symptom development.
(3) Contrary to the classical description by Brion & Jedynak, our patient did not exhibit denial of ownership of the affected hand, indicating that this symptom may not be a consistent feature across all AHS cases.
(4) Interestingly, the patient's ACA and ACOM, the primary blood supply to the corpus callosum, were unaffected, as evidenced by the CTA.The observed MCA stenosis could not account for the extensive corpus callosum infarct.
(5) Despite the presence of posterior AHS features, no radiological evidence of thalamic, parietal, or occipital lobe involvement was found.The arm levitation presentation in our patient could also indicate paroxysmal kinesigenic dyskinesia (PKD), a rare disorder characterized by involuntary movements such as dystonia and choreoathetosis, precipitated by sudden movement or startle. 37However, several characteristics suggest that PKD is less likely than posterior AHS.Firstly, PKD attacks are typically triggered by abrupt movement, an increase in speed, amplitude, or strength, the sudden addition of new actions during ongoing steady movements, or a change in direction. 38In our case, the arm levitation was triggered only by walking-a step-wise, voluntary movement that did not involve sudden movement.The speed and direction of walking did not affect the manifestation of arm levitation.Secondly, the duration of PKD attacks is typically brief, mainly lasting less than a minute. 38In contrast, the arm levitation in our patient persisted throughout her ambulation.Thirdly, most cases of PKD are preceded by a premonition or aura, 37 which was absent in our patient.Lastly, new PKD attacks cannot be induced for a refractory period of approximately 20 minutes. 38However, arm levitation could easily manifest upon walking without any such refractory period in our patient.Therefore, the arm levitation in this patient aligns more with the posterior AHS presentation than with PKD.
The complex and diverse clinical manifestations of AHS have made anatomical localization challenging.Past studies have highlighted similar discrepancies between clinical presentation and radiological evidence.For instance, Pappalardo et al. 27 reported a case of parieto-occipital infarct that exhibited compulsive manipulation, difficulty in releasing tools, and IMC without any posterior AHS features.Similarly, Rafiei et al. 39 reported a case of posterior AHS following a left pontine hemorrhage.Although different subtypes of AHS have been distinguished, its clinical diversity has resulted in inconsistent and disputable classification systems. 4While the three-variant classification is commonly used, alternative classification systems have been proposed.Aboitiz et al., 40 for example, put forth a five-category classification system that includes: (i) diagonistic dyspraxia and related syndromes, (ii) alien hand, (iii) way-ward hand and related syndromes, (iv) supernumerary hands and (v) agonistic dyspraxia.Additionally, some researchers have suggested classifying AHS into motor (anterior AHS) and sensory (posterior AHS) variants. 4Scepkowski and Cronin-Golomb 41 underlined three factors that contribute to the difficulty in systematically studying the AHS: (1) Its rarity relative to other neurological disorders, forcing reliance on case reviews.This limits the ability to examine a large, diverse population of AHS patients, making it difficult to generalize findings and draw definitive conclusions.
(2) Its transient nature, in most cases, poses challenges for long-term study, complicating the process of capturing and measuring the full range of clinical manifestations.
(3) The coincidental occurrence of other behavioral dysfunctions, such as hemiparesis, motor neglect, or neglect of visual hemispace, hinders the assessment process.
These factors, combined with the lack of uniformity in assessment methods, including both behavioral and neuroimaging tests, impede the establishment of clear subtypes of alien-hand phenomena.
Different pathophysiological mechanisms likely contribute to the diverse behaviors observed in AHS. 4 Elucidating them requires a deep understanding of the functional anatomy of the highly intricate callosal network.Conventional radiological modalities such as CT and magnetic resonance imaging (MRI) do not have the capacity to visualize the interhemispheric CC fiber connections. 2The emergence of Diffusion Tensor Tractography (DTT) study in recent years has enabled a 3-dimensional visualization of the CC architecture and integrity, providing a more in-depth analysis into the clinical-anatomical correlation of AHS. 2,42olated and extensive CC infarcts are rare, with only a few reported cases.In 1999, Lausberg et al. 43 reported a case of CDS following an infarct of the total length of the corpus callosum, manifesting callosal AHS.Using comprehensive neuropsychological investigations, the authors demonstrated that despite left-handedness, the CDS is analogous to right-handers revealing left-hemispheric dominance for language and praxis.In 2011, Yuan et al. 4 described a case of mixed callosal-posterior AHS following an extensive corpus callosum infarct involving the genu, body, and splenium.The authors combined diffusion-weighted imaging (DWI) with magnetic resonance angiography (MRA) to determine the anatomical substrate underpinning the clinical presentation.In 2013, Jang et al. 2 reported a case of extensive corpus callosum infarct manifesting CDS and frontal-posterior AHS.In addition to neuropsychological testing, a DTT study was performed, followed by a comparison with the DTT findings of three normal subjects.The DTT revealed disruption of most interhemispheric CC fibers, except for those in the anterior genu and posterior splenium, congruent with the patient's neurological manifestation.In this report, the lesion was almost exclusively confined to the corpus callosum, sparing the frontal, parietal, and occipital lobes, and the thalamus.The unique neurological manifestations, therefore, can be attributed to the callosal network disruption, causing bihemispheric disinhibition or interhemispheric disconnection. 11he variations in AHS manifestation in these four reports solidify the hypothesis that even if the corpus callosum lesions are similar in location and extent, the symptom manifestations can still vary. 2is report is limited by the lack of neuropsychological and radiological evidence due to service unavailability.In our setting, a tertiary government hospital with heavy patient loads and limited resources, there is no in-house clinical psychologist.Additionally, MRI availability is restricted and reserved for a limited number of cases.Given that an MRI would not alter the management of the stroke itself, the request for an MRI in this case was not granted.The patient was advised to consider obtaining an MRI and neuropsychological evaluation at a private center; however, these investigations were not performed due to financial constraints.Consequently, our hypothesis that the late manifestation of arm levitation suggests a potential temporal progression in symptom development could not be further substantiated.Furthermore, DTT is not available in our setting.We believe that if given access to these resources, combining neuropsychological assessments with DTT investigations could significantly contribute to uncovering the underlying pathomechanism of AHS in our patient.
AHS may hinder rehabilitation and can easily be overlooked or misinterpreted. 32Recognizing AHS is vital because its different manifestations may require different therapeutic approaches. 6Due to its rarity, evidence-based rehabilitation interventions for AHS are scarce.To date, there are no approved or recommended therapies for AHS.Management strategies are based on anecdotal reports of both pharmacological and behavioral interventions.For the anterior variant, suggested interventions include sensory tricks, distracting tasks, CBT, and verbal cue.On the other hand, the posterior variant may benefit from treatments such as clonazepam, botulinum toxin, visualization strategies, and spatial recognition tasks. 11n mirror box therapy, the congruency between motor intention and visual feedback elicited by the vision of the intact hand moving through the mirror improves the voluntary control of the alien hand. 36However, due to reliance on sensorimotor integration, this approach may only work for posterior AHS, as anterior AHS seems to depend on a failure to inhibit motor behavior of the non-dominant hemisphere. 44Clonazepam possibly potentiates thalamic GABAergic circuitry, resulting in either reducing the arm's oversensitivity to external stimuli or dampening the internal stimulus driving the AHS. 15The limb restraint strategy likely provided enough stimulation for the sensory spinal grasp reflex to achieve accommodation, thus inhibiting the movement. 11Interestingly, in the case presented in this report, the IMC showed the best response to these interventions when compared to the other motor symptoms.
Educating the patient and caregiver is essential to managing AHS, as it can help them cope with the challenging behavior associated with this condition. 32Caregiver involvement plays a significant role in optimizing the rehabilitation outcome.
For instance, the verbal cue intervention necessitates a strong commitment from the caregiver to deliver the strategy consistently to achieve positive results.Addressing anxiety and fear is also crucial and may involve using anxiolytics and appropriate behavioral therapies guided by experienced psychiatrists and psychologists. 11Unfortunately, none of the discussed interventions have demonstrated long-term benefits.Ergo, impairment-focused and multidisciplinary interventions may be the most appropriate for managing AHS.
Our limited understanding of the AHS pathophysiology has complicated the accurate prediction of its natural history. 11revious studies have reported mixed prognoses.In some cases, there was a complete resolution of symptoms. 4,14,27,32owever, other reports documented the persistence of symptoms, despite some improvement. 6,25,32In the case presented here, although some motor symptoms persisted, they were neither disturbing nor impairing functionally.
In conclusion, mixed variant AHS is an exceptionally rare and intriguing neurological phenomenon.To our knowledge, this is the first report of an extensive corpus callosum infarct displaying features from all three recognized AHS variants as part of the CDS.This case underscores the unique and distinctive clinical variations and showcases a challenging correlation between clinical manifestations and neuroanatomical substrates.Despite being recognized as a clinical entity for over a century, establishing a clear correlation between anatomical and clinical findings in AHS remains elusive, 11 and current theories on its underlying mechanisms are largely speculative. 6Future research is essential to unravel the intricate neural connections and the precise function of the corpus callosum.This can be best achieved by combining comprehensive neuropsychological testing with DTT studies.Refining AHS classification systems will be crucial as research continues to uncover the underlying pathomechanism and anatomical correlates.Additionally, there is a need for the development of a validated tool to standardize the AHS assessment, and the limited evidence available on rehabilitation interventions warrants further exploration.By fostering continued investigation and collaboration, we can deepen our understanding of AHS and enhance therapeutic options for those affected by this rare and enigmatic neurological disorder.
3) Under Outpatient rehabilitation, the top paragraph indicates that the patient's left hand would rise (levitation) that occurred specifically during walking.While this does indeed suggest the posterior form of alien hand, this also suggests a form of paroxysmal kinesigenic dyskinesia.These may not be mutually exclusive diagnoses; I suggest review this possible alternate diagnosis.Reviewer Expertise: Multiple sclerosis rehabilitation, functional neurological disorder study, case reports of alien hand syndrome.
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
Thank you for this valuable information that we missed.Information on the Van Vleuten paper is scarce, and most papers only briefly reference the article, including the reference you suggested.We have amended the information on the earliest reported cases of AHS by referencing Van Vleuten's study.The report by Van Vleuten can be found in the following sentences: "…..first described by Van Vleuten……" (Abstract) "It was first described by Van Vleuten in 1907 in a patient with a left-hemisphere brain tumor that had invaded the corpus callosum and exhibited right-hand grasping."(Page 3, lines 18-20) "AHS has been a subject of intrigue in the neurological community since its initial description by Van Vleuten more than a century ago."(Page 6, lines 138-139) 2. Under Patient Rehabilitation, the passage that the patient had a "left-sided hemisensory loss," but without details.Unclear whether this reflected light touch, pin, or otherwise.

Response
We have added the information to the revised manuscript: "Additionally, there was left-sided hemisensory loss in both pin-prick and light touch sensation but intact proprioception,….." (Page 5, lines 76-78) 3. Under Outpatient rehabilitation, the top paragraph indicates that the patient's left hand would rise (levitation) that occurred specifically during walking.While this does indeed suggest the posterior form of alien hand, this also suggests a form of paroxysmal kinesigenic dyskinesia.These may not be mutually exclusive diagnoses; I suggest review this possible alternate diagnosis.

Response
Thank you for the suggestion.We have expanded the discussion on the arm levitation and the consideration of PKD as a differential diagnosis: "The arm levitation presentation in our patient could also indicate paroxysmal kinesigenic dyskinesia (PKD), a rare disorder characterized by involuntary movements such as dystonia and choreoathetosis, precipitated by sudden movement or startle (new reference no.2).However, several characteristics suggest that PKD is less likely than posterior AHS.Firstly, PKD attacks are typically triggered by abrupt movement, an increase in speed, amplitude, or strength, the sudden addition of new actions during ongoing steady movements, or a change in direction (new reference no.3).In our case, the arm levitation was triggered only by walking-a step-wise, voluntary movement that did not involve sudden movement.The speed and direction of walking did not affect the manifestation of arm levitation.Secondly, the duration of PKD attacks is typically brief, mainly lasting less than a minute (new reference no.3).In contrast, the arm levitation in our patient persisted throughout her ambulation.Has a neuropsychological evaluation been performed to assess the cognitive domains involved?It could have been very useful for an assessment at baseline and to evaluate improvements.

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Finally, how do you explain the occurrence of AL so far from the acute event?, Please explain these aspects in more detail.

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Otherwise, the article is very interesting, informative and well-written.We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.
Author Response 11 Jun 2024

Khin Nyein Yin
Thank you for your positive review.We appreciate the comments and have provided responses to your inquiries below: 1.It would be important to understand the timing of the second CT scan and why an MRI was not performed.An MRI would certainly have given further information about the features and anatomical sites involved. Response: The second CT was done on the day the patient had a drop in her GCS.We have added this information to the text: "A repeat CT scan was done urgently on the same day and displayed…."(Page 4, line 50) An MRI was not performed due to service limitations.We expanded the study limitations in a separate paragraph: "In our setting, a tertiary government hospital with heavy patient loads and limited resources, there is no in-house clinical psychologist.Additionally, MRI availability is restricted and reserved for a limited number of cases.Given that an MRI would not alter the management of the stroke itself, the request for an MRI in this case was not granted.The patient was advised to consider obtaining an MRI and neuropsychological evaluation at a private center; however, these investigations were not performed due to financial constraints."(Page 10, lines 233-239) 2. Has a neuropsychological evaluation been performed to assess the cognitive domains involved?It could have been very useful for an assessment at baseline and to evaluate improvements The benefits of publishing with F1000Research: Your article is published within days, with no editorial bias • You can publish traditional articles, null/negative results, case reports, data notes and more • The peer review process is transparent and collaborative • Your article is indexed in PubMed after passing peer review • Dedicated customer support at every stage • For pre-submission enquiries, contact research@f1000.com

Figure 1 .
Figure 1.Axial view of the CT Brain.The CT images demonstrate hypodensity over the corpus callosum extending from the right genu to the left side of the splenium and the right temporal lobe.CT, computed tomography.

Figure 2 .
Figure 2. Sagittal [(a) & (b)] and coronal [(c) & (d)] views of the CT Brain.The CT images demonstrate an extensive hypodensity from genu to the splenium of the corpus callosum and the right temporal lobe.CT, computed tomography.

References 1 .
Graff-Radford NR, Welsh K, Godersky J: Callosal apraxia.Neurology.1987; 37 (1): 100-5 PubMed Abstract | Publisher Full Text Is the background of the case's history and progression described in sufficient detail?Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?Yes Is the case presented with sufficient detail to be useful for other practitioners?Yes Competing Interests: No competing interests were disclosed.

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Is the background of the case's history and progression described in sufficient detail?PartlyAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?PartlyIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?YesIs the case presented with sufficient detail to be useful for other practitioners?Yes Competing Interests: No competing interests were disclosed.

Table 1 .
Summary of reported cases of mixed variant alien hand syndrome.
Thirdly, most cases of PKD are preceded by a premonition or aura (new reference no. 2), which was absent in our patient.Lastly, new PKD attacks cannot be induced for a refractory period of approximately 20 minutes (new reference no.3).However, arm levitation could easily manifest upon walking without any such refractory period in our patient.Therefore, the arm levitation in this patient aligns more with the posterior AHS presentation than with PKD." (Page 8-9, lines 161-177) https://doi.org/10.5256/f1000research.146853.r266220